More on carcinogenesis

Recent advances in research on carcinogenesis, especially the identification of the oncogene, may have identified new and rather complicated mechanisms, but the effect has been to simplify our understanding by providing common pathways and unitary, comprehensible mechanisms by which many causes may act. The principle categories of causes may be identified as heredity, chemical exposure, viral infection, and radiation exposure.

As understanding of the basic mechanisms of cancer improves, concepts of chemical carcinogenesis have also grown more refined. A deep understanding of the biology of cancer helps to explain many of the phenomena critical to regulation, such as latency periods and cancer promotion. The divergence in goodness-of-fit to available response data results from differences in the assumptions involving adaptive mechanisms, threshold effects, receptor behavior, and transport to the target organ. Similarly, the population response to exposure to chemical carcinogens at low exposure levels depends on whether a “one-hit” model or an interactive model is operative.

Toxicity testing

The usual approach to assessing the toxicity of a new chemical or an agent that recently come under suspicion is to conduct a sequence of studies, each level of which is called a “tier”. A tier-one study, for example, may involve the use of in vitro studies, such as the Ames assay, in an effort to identify potential carcinogens early and to exclude them from further consideration as a possible product. A tier-two study might involve determination of LD₅₀ or LC₅₀ in animals.

As the tests become more sophisticated and the outcomes become more difficult to detect, they become much more expensive. Alternatives to animal studies are becoming available for specific purposes, but they cannot replace in vivo testing for all needs.

A major issue in selecting any kind of animal model is the biological relevance of the model to the application intended. The experiment must be at least comparable to human routes of exposure, metabolic pathways, and the potential for expression of the effect.

From Essentials of Medical Geology. Elsevier Inc., 2005.

Wordlist

Biomagnification	бионакопление, биоаккумуляция
Bolus	пищевая масса, кусок пищи
By-product	побочный продукт
Eliminate	устранять
Excretion	выведение, экскреция
Exposure	подвергание воздействию, экспозиция
Food web	пищевая сеть
Framework	структура, точка отсчета
Hazard	опасность, риск
Host	организм-хозяин, реципиент
Host defences	иммунная защита организма
Infusion	вливание, введение
Ingestion	прием пищи, глотание
Input	ввод, вход
Intravenous	внутривенный
Metabolite	метаболит, продукт обмена веществ
Pathway	путь, прохождение, траектория
Risk assessment	оценка рисков
Scope	рамки, границы
Sequestration	секвестрация, отторжение
Target organ	орган-мишень
Tissue	ткань
Uptake	поглощение, ввод
Xenobiotic	ксенобиотик, чужеродное вещество